Injuries to the central nervous system (CNS) are among the most devastating and costly of human afflictions. Recent advances in science and technology now provide tools which, for the first time, permit methodical approaches to repair or regenerate damaged CNS axons. Such tools include, among others, a variety of neurotrophic and signaling factors, cellular adhesion molecules, disinhibiting agents, cell and gene-based therapies, and reliable animal models of neurotrauma. Several laboratories have reported encouraging progress in applying such interventions to enhance axonal regeneration and functional recovery following CNS injury. A key challenge in the further development of such therapies is the need to develop delivery systems which are optimal for the specific intervention and the target tissue. Phase I of this grant proposes to develop substrates incorporating a novel class of synthetic biomaterials, based on the self-assembly of oligopeptides in physiological solutions. These materials possess a wide range of desirable physical and biological attributes, and offer potentially unique advantages in the design of therapeutic delivery systems for the CNS and other organ systems. Phase I will optimize the materials design and specifications for such applications- in preparation for Phase II in vivo studies. PROPOSED COMMERCIAL APPLICATIONS The unique biomaterials to be developed in this grant have potentially broad applications as substrates for targeted delivery of therapeutic interventions, both in the nervous system and other organ systems. Neurological injuries and degenerative diseases of the nervous system alone are estimated to affect over 7 million Americans and to represent over $90 billion in annual costs to society in the U.S. The overall direct costs of care just for spinal cord injury in the U.S. are approximately $8 billion a year. As core substrates, these materials may potentially accelerate development of a wide spectrum of implantable cellular and molecular-based therapies for tissue repair, with commensurately large. commercial, medical and social impact.